The contribution of adult hippocampal neurogenesis,'as well the entire hippocampal dentate gyrus, to cocaine addiction and relapse is currently unknown. Using a rat model of drug dependence, i.v. cocaine selfadministration, I have identified that the number of doublecortin-positive (DCX+) immature neurons in the dentate gyrus is increased after cocaine self-administration despite subsequent withdrawal or continued drug taking. This indicates that an increased number of DCX+ neurons in the dentate gyrus may be a neuroadaptation that contributes to cocaine addiction and relapse. To expand on these results and specifically explore changes in protein expression that may mediate this increased number of DCX+ neurons, for Aim 1 I will perform immunoblotting on dentate gyrus tissue dissections to identify proteins that change in expression in after cocaine self-administration and withdrawal. I also show pilot data with promising evidence that brain-derived neurotrophic factor (BDNF) decreases in expression after withdrawal from cocaine self-administration. Therefore, for Aim 2 I will infuse BDNF (and/or other proteins identified in Aim 1) into the dentate gyrus. In Aim 2a, I will examine cocaine self-administration and reinstatement behaviors. I hypothesize that normalization of protein expression in the dentate gyrus after cocaine selfadministration will attenuate cocaine-taking and cocaine-seeking behaviors. In Aim 2b, I will determine if normalization of BDNF expression in the dentate gyrus normalizes the increase in DCX+ neurons, a critical step towards assessing a causative link between adult neurogeneis and addictive behaviors. [unreadable] [unreadable] This research has potential to advance our understanding of how the brain changes after addiction, and what changes in the brain may be obstacles to long term abstinence from drug taking. My research will provide insight in whether the manipulation of adult hippocampal neurogenesis, or the birth of new neurons in the adult brain, holds potential for treating cocaine addiction and encouraging abstinence. Aside from adult neurogenesis, my research may also generate new avenues for addiction treatment in that it will assess a wide variety of proteins that change in the hippocampal dentate gyrus after cocaine selfadministration and withdrawal. [unreadable] [unreadable] [unreadable]